Details of Disease

General Information of Disease (ID: DISMKWS3)

Disease Name	Long QT syndrome
Synonyms	ventricular arrhythmia associated with long QT syndrome; long QT syndrome; long Q-T syndrome; LQT
Disease Class	BC65: Genetic cardiac arrhythmia
Definition	A condition that is characterized by episodes of fainting (syncope) and varying degree of ventricular arrhythmia as indicated by the prolonged QT interval. The inherited forms are caused by mutation of genes encoding cardiac ion channel proteins. The two major forms are Romano-Ward syndrome (also known as long QT syndrome 1) and Jervell-Lange Nielsen syndrome.
Disease Hierarchy	DIS6SVEE: Syndromic disease DISQBA23: Congenital heart disease DISMKWS3: Long QT syndrome
ICD Code	ICD-11 ICD-11: BC65.0 ICD-10 ICD-10: I49, I49.8 Expand ICD-11 'BC65.0 Expand ICD-10 'I49; 'I49.8
Disease Identifiers	MONDO ID MONDO_0002442 MESH ID D008133 UMLS CUI C0023976 MedGen ID 44193 SNOMED CT ID 9651007

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

This Disease is Treated as An Indication in 6 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Aprindine	DMBXWU8	Approved	Small molecular drug	[1]
Bretylium	DM1FX74	Approved	Small molecular drug	[2]
Disopyramide	DM5SYZP	Approved	Small molecular drug	[3]
Lidocaine	DML4ZOT	Approved	Small molecular drug	[4]
Moricizine	DMOMBJW	Approved	Small molecular drug	[5]
Oxprenolol	DM51OQW	Approved	Small molecular drug	[6]
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⏷ Show the Full List of 6 Drug(s)

This Disease is Treated as An Indication in 1 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
GS-6615	DMGJQVI	Phase 3	Small molecular drug	[7]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 23 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CACNA1D	TT7RGTM	Limited	Biomarker	[8]
KCNB1	TT5OEKU	Limited	Genetic Variation	[9]
KCNJ2	TTH7UO3	Limited	Autosomal dominant	[10]
MYBPC3	TT9WOBN	Limited	Genetic Variation	[11]
KCNJ5	TTEO25X	Disputed	Autosomal dominant	[10]
KCNQ2	TTPXI3S	Disputed	Genetic Variation	[12]
KCNQ4	TT8HGRW	Disputed	Genetic Variation	[12]
KCNA5	TTW0CMT	moderate	Genetic Variation	[13]
KCNK3	TTGR91N	moderate	Genetic Variation	[13]
ABCC9	TTEF5MJ	Strong	Genetic Variation	[14]
GJA5	TTFQKZ7	Strong	Biomarker	[15]
GJB3	TTVRQ8L	Strong	Biomarker	[16]
KCND3	TTPLQO0	Strong	Biomarker	[17]
KCNJ11	TT329V4	Strong	Genetic Variation	[14]
KCNJ2	TTH7UO3	Strong	Genetic Variation	[18]
KCNJ5	TTEO25X	Strong	Genetic Variation	[19]
KCNJ9	TT4VHL6	Strong	Genetic Variation	[19]
KCNQ3	TTIVDM3	Strong	Genetic Variation	[12]
MYH7	TTNIMDP	Strong	Genetic Variation	[20]
RPGR	TTHBDA9	Strong	Biomarker	[21]
SCN10A	TT90XZ8	Strong	Genetic Variation	[22]
SQLE	TTE14XG	Strong	Biomarker	[23]
TDP2	TTYF26D	Strong	Genetic Variation	[24]
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⏷ Show the Full List of 23 DTT(s)

This Disease Is Related to 3 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
CACNA1C	DTAIV1Z	Moderate	Autosomal dominant	[10]
KCNH2	DTD0BMQ	Definitive	Autosomal dominant	[10]
KCNQ1	DTYE3RN	Definitive	Autosomal dominant	[10]
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This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
CYP1A1	DE6OQ3W	Limited	Biomarker	[25]
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This Disease Is Related to 42 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CACNB3	OTP30DIU	Limited	Biomarker	[8]
CAV3	OTWSFDB4	Limited	Autosomal dominant	[10]
KCND2	OTIFUVV7	Limited	Genetic Variation	[26]
KCNJ2	OT2OQEZS	Limited	Autosomal dominant	[10]
MINK1	OTKB0RA8	Limited	Genetic Variation	[27]
RNF207	OT9AYVGV	Limited	Autosomal dominant	[28]
SCN1B	OTGD78J3	Limited	Genetic Variation	[29]
SSUH2	OTWUBDV0	Limited	CausalMutation	[30]
AKAP9	OT7Z2YRP	Disputed	Autosomal dominant	[10]
ANK2	OTWB4R1Y	Disputed	Autosomal dominant	[10]
KCNE2	OTUO214Y	Disputed	Autosomal dominant	[10]
KCNJ5	OTA2MBIE	Disputed	Autosomal dominant	[10]
SCN4B	OT3JSUWO	Disputed	Autosomal dominant	[10]
SNTA1	OTUICTGZ	Disputed	Autosomal dominant	[10]
ALG10	OTM1ATVR	moderate	Genetic Variation	[31]
ALG10B	OTAHWAKE	moderate	Genetic Variation	[31]
CACNA1C	OT6KFNMS	Moderate	Autosomal dominant	[10]
KCNA4	OTTIGYN7	moderate	Genetic Variation	[13]
KCNE3	OTKWKR91	moderate	Biomarker	[32]
NOS1AP	OTDFOBRU	moderate	Genetic Variation	[33]
RYR2	OT0PF19E	moderate	Genetic Variation	[34]
ACADM	OTA4P0FC	Strong	Biomarker	[35]
ACSBG1	OTM040MW	Strong	Biomarker	[36]
CAVIN1	OTFO915U	Strong	Genetic Variation	[37]
CNTN3	OTC1274J	Strong	Biomarker	[38]
COL4A5	OTHG60RE	Strong	Biomarker	[39]
CRX	OTH435SV	Strong	Biomarker	[21]
CUZD1	OTDQJVZ8	Strong	Biomarker	[23]
FLNC	OT3F8J6Y	Strong	Biomarker	[40]
KCNE5	OTF4JYGZ	Strong	Biomarker	[41]
LYPD4	OTYNO8BS	Strong	Biomarker	[42]
ND1	OTCLGIXV	Strong	Genetic Variation	[43]
PELI1	OTMLBCLC	Strong	Genetic Variation	[20]
PICALM	OTQVRPMQ	Strong	Genetic Variation	[44]
PRDM6	OTKY12D9	Strong	Genetic Variation	[20]
SLN	OTERIU75	Strong	Biomarker	[45]
SNAP91	OTE3EXWZ	Strong	Genetic Variation	[44]
TBX20	OTMPU2XQ	Strong	Genetic Variation	[46]
TRDN	OTXVE9SF	Strong	Autosomal recessive	[10]
CALM1	OTNYA92F	Definitive	Autosomal dominant	[10]
KCNH2	OTZX881H	Definitive	Autosomal dominant	[10]
KCNQ1	OT8SPJNX	Definitive	Autosomal dominant	[10]
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⏷ Show the Full List of 42 DOT(s)

References

1	Time-to-Onset Analysis of Drug-Induced Long QT Syndrome Based on a Spontaneous Reporting System for Adverse Drug Events. PLoS One. 2016 Oct 10;11(10):e0164309.
2	Bretylium FDA Label
3	Disopyramide FDA Label
4	Lidocaine FDA Label
5	Moricizine FDA Label
6	Oxprenolol FDA Label
7	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
8	The structures of the human calcium channel alpha 1 subunit (CACNL1A2) and beta subunit (CACNLB3) genes.Genomics. 1995 May 20;27(2):312-9. doi: 10.1006/geno.1995.1048.
9	A hydrophobicity-dependent motif responsible for surface expression of cardiac potassium channel.Cell Signal. 2009 Feb;21(2):349-55. doi: 10.1016/j.cellsig.2008.11.006. Epub 2008 Nov 13.
10	Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
11	Multiplex targeted high-throughput sequencing for Mendelian cardiac disorders.Clin Genet. 2014 Apr;85(4):365-70. doi: 10.1111/cge.12168. Epub 2013 May 13.
12	Nervous system KV7 disorders: breakdown of a subthreshold brake.J Physiol. 2008 Apr 1;586(7):1791-801. doi: 10.1113/jphysiol.2008.150656. Epub 2008 Jan 31.
13	Clinical aspects of type-1 long-QT syndrome by location, coding type, and biophysical function of mutations involving the KCNQ1 gene.Circulation. 2007 May 15;115(19):2481-9. doi: 10.1161/CIRCULATIONAHA.106.665406. Epub 2007 Apr 30.
14	Multiple single-nucleotide polymorphisms (SNPs) in the Japanese population in six candidate genes for long QT syndrome.J Hum Genet. 2001;46(3):158-62. doi: 10.1007/s100380170106.
15	Functional suppression of Kcnq1 leads to early sodium channel remodelling and cardiac conduction system dysmorphogenesis.Cardiovasc Res. 2013 Jun 1;98(3):504-14. doi: 10.1093/cvr/cvt076. Epub 2013 Mar 29.
16	Benign familial neonatal convulsions (BFNC) resulting from mutation of the KCNQ2 voltage sensor.Eur J Hum Genet. 2000 Dec;8(12):994-7. doi: 10.1038/sj.ejhg.5200570.
17	Mutation analysis of candidate genes SCN1B, KCND3 and ANK2 in patients with clinical diagnosis of long QT syndrome.Physiol Res. 2008;57(6):857-862. doi: 10.33549/physiolres.931184. Epub 2007 Nov 30.
18	Gene-Targeted Analysis of Clinically Diagnosed Long QT Russian Families.Int Heart J. 2017 Feb 7;58(1):81-87. doi: 10.1536/ihj.16-133. Epub 2016 Dec 21.
19	The phenotype characteristics of type 13 long QT syndrome with mutation in KCNJ5 (Kir3.4-G387R).Heart Rhythm. 2013 Oct;10(10):1500-6. doi: 10.1016/j.hrthm.2013.07.022. Epub 2013 Jul 18.
20	High-throughput single-strand conformation polymorphism analysis by automated capillary electrophoresis: robust multiplex analysis and pattern-based identification of allelic variants.Hum Mutat. 1999;13(4):318-27. doi: 10.1002/(SICI)1098-1004(1999)13:4<318::AID-HUMU9>3.0.CO;2-F.
21	A Systematic Review on the Cost-Effectiveness of Genetic and Electrocardiogram Testing for Long QT Syndrome in Infants and Young Adults.Value Health. 2015 Jul;18(5):700-8. doi: 10.1016/j.jval.2015.03.1788. Epub 2015 May 16.
22	Deleterious protein-altering mutations in the SCN10A voltage-gated sodium channel gene are associated with prolonged QT.Clin Genet. 2018 Apr;93(4):741-751. doi: 10.1111/cge.13036. Epub 2017 May 18.
23	Identification of two nervous system-specific members of the erg potassium channel gene family.J Neurosci. 1997 Dec 15;17(24):9423-32. doi: 10.1523/JNEUROSCI.17-24-09423.1997.
24	The beginnings of long QT syndrome.Curr Opin Cardiol. 2015 Jan;30(1):112-7. doi: 10.1097/HCO.0000000000000135.
25	Relationship of blood aryl hydrocarbon receptor mRNA and cytochrome P450 1A1 mRNA expression with corrected QT interval among residents exposed to arsenic via drinking water. Zhonghua Xin Xue Guan Bing Za Zhi. 2016 Mar;44(3):260-4.
26	Mutations in the genes KCND2 and KCND3 encoding the ion channels Kv4.2 and Kv4.3, conducting the cardiac fast transient outward current (ITO,f), are not a frequent cause of long QT syndrome.Clin Chim Acta. 2005 Jan;351(1-2):95-100. doi: 10.1016/j.cccn.2004.08.017.
27	A novel long-QT 5 gene mutation in the C-terminus (V109I) is associated with a mild phenotype.J Mol Med (Berl). 2001 Sep;79(9):504-9. doi: 10.1007/s001090100249.
28	Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
29	A missense mutation in the sodium channel 1b subunit reveals SCN1B as a susceptibility gene underlying long QT syndrome.Heart Rhythm. 2014 Jul;11(7):1202-9. doi: 10.1016/j.hrthm.2014.03.044. Epub 2014 Mar 21.
30	Rippling is not always electrically silent in rippling muscle disease.Muscle Nerve. 2011 Apr;43(4):601-5. doi: 10.1002/mus.21947.
31	A KCR1 variant implicated in susceptibility to the long QT syndrome.J Mol Cell Cardiol. 2011 Jan;50(1):50-7. doi: 10.1016/j.yjmcc.2010.10.007. Epub 2010 Oct 13.
32	Novel KCNE3 mutation reduces repolarizing potassium current and associated with long QT syndrome.Hum Mutat. 2009 Apr;30(4):557-63. doi: 10.1002/humu.20834.
33	Generation of the human induced pluripotent stem cell (hiPSC) line PSMi007-A from a Long QT Syndrome type 1 patient carrier of two common variants in the NOS1AP gene.Stem Cell Res. 2019 Apr;36:101416. doi: 10.1016/j.scr.2019.101416. Epub 2019 Mar 6.
34	Differential Diagnosis Between Catecholaminergic Polymorphic Ventricular Tachycardia and Long QT Syndrome Type 1- Modified Schwartz Score.Circ J. 2018 Aug 24;82(9):2269-2276. doi: 10.1253/circj.CJ-17-1032. Epub 2018 Jun 21.
35	The sudden infant death syndrome gene: does it exist?.Pediatrics. 2004 Oct;114(4):e506-12. doi: 10.1542/peds.2004-0683.
36	A wearable remote monitoring system for the identification of subjects with a prolonged QT interval or at risk for drug-induced long QT syndrome.Int J Cardiol. 2018 Sep 1;266:89-94. doi: 10.1016/j.ijcard.2018.03.097.
37	Fatal cardiac arrhythmia and long-QT syndrome in a new form of congenital generalized lipodystrophy with muscle rippling (CGL4) due to PTRF-CAVIN mutations. PLoS Genet. 2010 Mar 12;6(3):e1000874. doi: 10.1371/journal.pgen.1000874.
38	Health status of cardiac genetic disease patients and their at-risk relatives.Int J Cardiol. 2013 May 25;165(3):448-53. doi: 10.1016/j.ijcard.2011.08.083. Epub 2011 Sep 17.
39	Electrocardiographic features in Andersen-Tawil syndrome patients with KCNJ2 mutations: characteristic T-U-wave patterns predict the KCNJ2 genotype.Circulation. 2005 May 31;111(21):2720-6. doi: 10.1161/CIRCULATIONAHA.104.472498. Epub 2005 May 23.
40	Filamin C: a novel component of the KCNE2 interactome during hypoxia.Cardiovasc J Afr. 2016 Jan-Feb;27(1):4-11. doi: 10.5830/CVJA-2015-049.
41	Does KCNE5 play a role in long QT syndrome?.Clin Chim Acta. 2004 Jul;345(1-2):49-53. doi: 10.1016/j.cccn.2004.02.033.
42	Mortality of inherited arrhythmia syndromes: insight into their natural history.Circ Cardiovasc Genet. 2012 Apr 1;5(2):183-9. doi: 10.1161/CIRCGENETICS.111.961102. Epub 2012 Feb 28.
43	A mitochondrial DNA mutation cosegregates with the pathophysiological U wave.Biochem Biophys Res Commun. 1999 Apr 2;257(1):228-33. doi: 10.1006/bbrc.1999.0443.
44	Calmodulin mutations and life-threatening cardiac arrhythmias: insights from the International Calmodulinopathy Registry. Eur Heart J. 2019 Sep 14;40(35):2964-2975. doi: 10.1093/eurheartj/ehz311.
45	The variation of the sarcolipin gene (SLN) in atrial fibrillation, long QT syndrome and sudden arrhythmic death syndrome.Clin Chim Acta. 2007 Jan;375(1-2):87-91. doi: 10.1016/j.cca.2006.06.020. Epub 2006 Jun 22.
46	Tbx20 controls the expression of the KCNH2 gene and of hERG channels.Proc Natl Acad Sci U S A. 2017 Jan 17;114(3):E416-E425. doi: 10.1073/pnas.1612383114. Epub 2017 Jan 3.